Treatment with dovitinib in patients with liver cancer before local treatment: a phase II study

• Conditions: Hepatocellular carcinoma, not metastatic; MedDRA version: 14.0Level: LLTClassification code 10019830Term: Hepatocellular carcinoma resectableSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 14.0Level: LLTClassification code 10019828Term: Hepatocellular carcinoma non-resectableSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2011-002445-36-NL
• Lead Sponsor: Department of Clinical Oncology, Leiden University Medical Center

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2011-08-31
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

1.Histological or cytological confirmed HCC or HCC diagnosed by the Barcelona criteria.
2.HCC stage A or B according to the Barcelona Clinic Liver Cancer (BCLC) staging classification (appendix 2; Llovet et al, 2008a).
3.Patients eligible for local therapy, i.e. RF-ablation, chemo-embolization, or surgical resection
4.ECOG (WHO) performance status 0, 1, or 2
5.Age = 18 years old
6.At least one uni-dimensional measurable lesion. Lesions must be measured by CT-scan or MRI-scan
7.Patients must have adequate bone marrow, liver and renal function as assessed by the following laboratory requirements:
•Absolute neutrophil count (ANC) = 1.5 x 109/L
•Platelets = 75 x 109/L
•Hemoglobin (Hgb) = 6.0 mmol/L
•Serum total bilirubin: = 1.5 x ULN
•Child-Pugh score of up to 6 points, i.e. Child-Pugh classe A (appendix 3), with no encephalopathy. Child-Pugh status must be calculated based on clinical findings and laboratory results during the baseline/screening period
•ALT and AST = 3.0 x ULN (with or without liver metastases)
•Serum creatinine = 1.5 x ULN or serum creatinine >1.5 – 3 x ULN if calculated creatinine clearance (CrCl) is = 30 mL/min using the Cockroft-Gault equation, see formula below:
CrCl = [140-age (years)] x weight (kg) / [72 x serum Cr (mg/dL)]
(if patient is female multiply the above by 0.85)
8.Life expectancy of at least 3 months
9.Patients who give a written informed consent obtained according to local guidelines

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 15
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 5

Exclusion Criteria

1.Patients with brain metastases or who have signs/symptoms attributable to brain metastases and have not been assessed with radiologic imaging to rule out the presence of brain metastases
2.Patients with another primary malignancy within 3 years prior to starting study drug, with the exception of adequately treated in-situ carcinoma of the uterine cervix, skin cancer (such as basal cell carcinoma, squamous cell carcinoma, or non-melanomatous skin cancer), or superficial bladder tumors (Ta, Tis, and T1)
3.Patients who have received the last administration of an anticancer therapy including chemotherapy, immunotherapy, hormonal therapy and monoclonal antibodies (but excluding nitrosurea, mitomycin-C, targeted therapy and radiation) = 4 weeks prior to starting study drug, or who have not recovered from the side effects of such therapy
4.Patients who have received the last administration of nitrosurea or mitomycin-C = 6 weeks prior to starting study drug, or who have not recovered from the side effects of such therapy
5.Patients who have received targeted therapy (e.g. sunitinib, sorafenib, pazopanib) = 2 weeks prior to starting study drug, or who have not recovered from the side effects of such therapy
6.Patients who have had radiotherapy = 4 weeks prior to starting study drug, or = 2 weeks prior to starting study drug in the case of localized radiotherapy (e.g. for analgesic purpose or for lytic lesions at risk of fracture), or who have not recovered from radiotherapy toxicities
7.Patients who have undergone major surgery (e.g. intra-thoracic, intra-abdominal or intra-pelvic), open biopsy or significant traumatic injury = 4 weeks prior to starting study drug, or patients who have had minor procedures, percutaneous biopsies or placement of vascular access device = 1 week prior to starting study drug, or who have not recovered from side effects of such procedure or injury
8.Patients with any of the following concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study:
•Impaired cardiac function or clinically significant cardiac diseases, including any of the following:
a.History or presence of serious uncontrolled ventricular arrhythmias
b.Clinically significant resting bradycardia
c.LVEF assessed by 2-D echocardiogram (ECHO) < 50% or lower limit of normal (which ever is higher) or multiple gated acquisition scan (MUGA) < 45% or lower limit of normal (which ever is higher)
d.Any of the following within 6 months prior to starting study drug: myocardial infarction (MI), severe/unstable angina, Coronary Artery Bypass Graft (CABG), Congestive Heart Failure (CHF), Cerebrovascular Accident (CVA), Transient Ischemic Attack (TIA), Pulmonary Embolism (PE)
e.Uncontrolled hypertension defined by a SBP = 160 mm Hg and/or DBP = 100 mm Hg, with or without anti-hypertensive medication(s)
•Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of dovitinib (e.g. ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection)
•Known diagnosis of human immunodeficiency virus (HIV) infection (HIV testing is not mandatory)
•Patients who are currently receiving anticoagulation treatment with therapeutic doses of warfarin
•Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g. active or uncontrolled infection, uncontrolle

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified